The application of RASSF1A promoter methylation as a biomarker in breast cancer: A comprehensive literature review

Hua Geng*, Longtao Wu

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


Frequent hypermethylation of RASSF1A promoter has been reported to account for its expression silencing in multiple human malignancies including breast cancer. The methylated RASSF1A was found both in cancer tissues and in paired serum DNA samples of breast cancer patients, but was rare in the serum of non-neoplastic counterparts. In addition, RASSF1A methylation appears to correlate with poor prognostic features and impaired survival of cancer patients, thus indicating RASSF1A promoter methylation could serve as a useful and valuable biomarker for cancers. We made a comprehensive systemic review of publications in the past 15 years. With the meta-analysis and identification of outlier studies that significantly contributed to between-study heterogeneity, we reach the following conclusion: 1) Methylation of RASSF1A promoter could happen in adjacent normal samples. And it should be cautious to use well-validated adjacent normal samples as reference in study the methylation of RASSF1A in breast cancer patients. 2) Methylation of RASSF1A promoter is an early event in breast cancer development. And most importantly, its methylation remains constant across all stages during breast cancer development. 3) Methylation of RASSF1A promoter is positively associate with ER and PR status, but not with HER2 and LN status. That is, the methylation of RASSF1A promoter is lower in triple-negative subtype of breast cancer. 4) RASSF1A methylation in body fluid including serum and nipple fluid is usefully but with limited sensitivity. 5) Peripheral blood leukocytes or white blood cell genomic DNA is not suitable to be used as control for RASSF1A promoter methylation in breast cancer patients. Through the systemic review of the RASSF1A promoter methylation studies, we not only summarize the current discoveries; also, we pinpoint the pitfalls in the application of RASSF1A as biomarker for diagnosis or prognosis purposes.

Original languageEnglish (US)
Pages (from-to)7729-7742
Number of pages14
JournalInternational Journal of Clinical and Experimental Medicine
Issue number5
StatePublished - May 30 2016


  • Breast cancer
  • Epigenetics
  • Promoter methylation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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